Mechanistic modeling and parameter-adaptive nonlinear model predictive control of a microbioreactor

Abstract

Microbioreactors are a promising technology to accelerate biologic drug development. In aerobic cellular respiration, a potential limit to the productivity of such systems is the transport of oxygen from an ex-ternal gas to the most oxygen-deficient cells, and the potential for excessive spatially localized dissolved oxygen which can result in cellular damage. This article analytically solves a mechanistic model for the spatiotemporal transport of oxygen through a gas-permeable membrane to the cells within a microbiore-actor. An analytical solution to the partial differential equations for oxygen transport is derived using the finite Fourier transform method. A parameter-adaptive extended Kalman filter is shown to produce highly accurate estimates of the oxygen uptake rate of the cells, with some fluctuation in estimates of the spe-cific cell growth rate and the specific oxygen uptake rate. The estimates are fed to a model predictive control formulation that improves the spatial control of dissolved oxygen during cell growth by more than 30% compared to a PID controller. (c) 2021 Elsevier Ltd. All rights reserved.